CD4/CD8 double-negative mycosis fungoides: a review


Submitted: 15 December 2023
Accepted: 15 February 2024
Published: 12 April 2024
Abstract Views: 76
PDF: 25
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

Mycosis Fungoides (MF) stands as the predominant form of primary cutaneous T-cell lymphoma (CTCL). It manifests a diverse array of clinical, histological, and immunophenotypic variations, each bearing distinct prognostic implications. The typical immunophenotypic profile of mycosis fungoides involves CD3+/CD4+/CD45RO+ memory T cells. Notably, the CD4-/CD8- double-negative variant of MF is a rare occurrence, observed in approximately 12% of early-stage cases and more prevalent in tumor-stage instances, often correlated with atypical clinical presentations. Despite its rarity, scant information is available about double-negative Mycosis Fungoides, with only a limited number of cases documented in the existing literature. This review aims to provide enhanced clarity, comprehension, and a detailed exploration of the spectrum encompassing double-negative mycosis fungoides.


Willemze R, Jaffe ES, Burg G, Cerroni L, Berti E, Swerdlow SH, Ralfkiaer E, Chimenti S, Diaz-Perez JL, Duncan LM, Grange F, Harris NL, Kempf W, Kerl H, Kurrer M, Knobler R, Pimpinelli N, Sander C, Santucci M, Sterry W, Vermeer MH, Wechsler J, Whittaker S, Meijer CJ. WHO-EORTC classification for cutaneous lymphomas. Blood. 2005 May 15;105(10):3768-85. doi: 10.1182/blood-2004-09-3502. Epub 2005 Feb 3. PMID: 15692063. DOI: https://doi.org/10.1182/blood-2004-09-3502

Bagherani N, Smoller BR. An overview of cutaneous T cell lymphomas. F1000Res. 2016 Jul 28;5:F1000 Faculty Rev-1882. doi: 10.12688/f1000research.8829.1. PMID: 27540476; PMCID: PMC4965697. DOI: https://doi.org/10.12688/f1000research.8829.1

Girardi M, Heald PW, Wilson LD. The pathogenesis of mycosis fungoides. N Engl J Med. 2004 May 6;350(19):1978-88. doi: 10.1056/NEJMra032810. PMID: 15128898. DOI: https://doi.org/10.1056/NEJMra032810

Wilcox RA. Cutaneous T-cell lymphoma: 2016 update on diagnosis, risk-stratification, and management. Am J Hematol. 2016 Jan;91(1):151-65. doi: 10.1002/ajh.24233. Epub 2015 Nov 26. PMID: 26607183; PMCID: PMC4715621. DOI: https://doi.org/10.1002/ajh.24233

Fujii K. New Therapies and Immunological Findings in Cutaneous T-Cell Lymphoma. Front Oncol. 2018 Jun 4;8:198. doi: 10.3389/fonc.2018.00198. PMID: 29915722; PMCID: PMC5994426. DOI: https://doi.org/10.3389/fonc.2018.00198

Amorim GM, Niemeyer-Corbellini JP, Quintella DC, Cuzzi T, Ramos-E-Silva M. Clinical and epidemiological profile of patients with early stage mycosis fungoides. An Bras Dermatol. 2018 Jul-Aug;93(4):546-552. doi: 10.1590/abd1806-4841.20187106. PMID: 30066762; PMCID: PMC6063099. DOI: https://doi.org/10.1590/abd1806-4841.20187106

Kim YH, Liu HL, Mraz-Gernhard S, Varghese A, Hoppe RT. Long-term outcome of 525 patients with mycosis fungoides and Sezary syndrome: clinical prognostic factors and risk for disease progression. Arch Dermatol. 2003 Jul;139(7):857-66. doi: 10.1001/archderm.139.7.857. PMID: 12873880. DOI: https://doi.org/10.1001/archderm.139.7.857

Zinzani PL, Ferreri AJ, Cerroni L. Mycosis fungoides. Crit Rev Oncol Hematol. 2008 Feb;65(2):172-82. doi: 10.1016/j.critrevonc.2007.08.004. Epub 2007 Oct 22. PMID: 17950613. DOI: https://doi.org/10.1016/j.critrevonc.2007.08.004

Furue M, Kadono T. New aspects of the clinicopathological features and treatment of mycosis fungoides and Sézary syndrome. J Dermatol. 2015 Oct;42(10):941-4. doi: 10.1111/1346-8138.13083. PMID: 26432429. DOI: https://doi.org/10.1111/1346-8138.13083

Martínez-Escala ME, González BR, Guitart J. Mycosis Fungoides Variants. Surg Pathol Clin. 2014 Jun;7(2):169-89. doi: 10.1016/j.path.2014.02.003. Epub 2014 Apr 13. PMID: 26837197. DOI: https://doi.org/10.1016/j.path.2014.02.003

Hodak E, David M, Maron L, Aviram A, Kaganovsky E, Feinmesser M. CD4/CD8 double-negative epidermotropic cutaneous T-cell lymphoma: an immunohistochemical variant of mycosis fungoides. J Am Acad Dermatol. 2006 Aug;55(2):276-84. doi: 10.1016/j.jaad.2006.01.020. PMID: 16844512. DOI: https://doi.org/10.1016/j.jaad.2006.01.020

Fierro MT, Novelli M, Savoia P, Cambieri I, Quaglino P, Osella-Abate S, Bernengo MG. CD45RA+ immunophenotype in mycosis fungoides: clinical, histological and immunophenotypical features in 22 patients. J Cutan Pathol. 2001 Aug;28(7):356-62. doi: 10.1034/j.1600-0560.2001.280704.x. PMID: 11437941. DOI: https://doi.org/10.1034/j.1600-0560.2001.280704.x

Massone C, Crisman G, Kerl H, Cerroni L. The prognosis of early mycosis fungoides is not influenced by phenotype and T-cell clonality. Br J Dermatol. 2008 Sep;159(4):881-6. doi: 10.1111/j.1365-2133.2008.08761.x. Epub 2008 Jul 17. PMID: 18644018. DOI: https://doi.org/10.1111/j.1365-2133.2008.08761.x

Cho-Vega JH, Tschen JA, Vega F. CD4/CD8 double-negative early-stage mycosis fungoides associated with primary cutaneous follicular center lymphoma. J Am Acad Dermatol. 2011 Oct;65(4):884-886. doi: 10.1016/j.jaad.2010.10.026. PMID: 21920253. DOI: https://doi.org/10.1016/j.jaad.2010.10.026

Kempf W, Kazakov DV, Cipolat C, Kutzner H, Roncador G, Tomasini D. CD4/CD8 double negative mycosis fungoides with PD-1 (CD279) expression--a disease of follicular helper T-cells? Am J Dermatopathol. 2012 Oct;34(7):757-61. doi: 10.1097/DAD.0b013e31825b26d1. PMID: 22722467. DOI: https://doi.org/10.1097/DAD.0b013e31825b26d1

Nagase K, Shirai R, Okawa T, Inoue T, Misago N, Narisawa Y. CD4/CD8 double-negative mycosis fungoides mimicking erythema gyratum repens in a patient with underlying lung cancer. Acta Derm Venereol. 2014 Jan;94(1):89-90. doi: 10.2340/00015555-1618. PMID: 23694996. DOI: https://doi.org/10.2340/00015555-1618

Ito A, Sugita K, Ikeda A, Yamamoto O. CD4/CD8 Double-negative Mycosis Fungoides: A Case Report and Literature Review. Yonago Acta Med. 2019 Mar 28;62(1):153-158. doi: 10.33160/yam.2019.03.021. PMID: 30962758; PMCID: PMC6437399. DOI: https://doi.org/10.33160/yam.2019.03.021

Shon U, Yun DK, Seong GH, Park BC, Kim MH, Lee DY. CD4/CD8 double-negative early-stage mycosis fungoides with CD30 expression. J Cutan Pathol. 2021 Apr;48(4):587-589. doi: 10.1111/cup.13846. Epub 2020 Sep 15. PMID: 32789870. DOI: https://doi.org/10.1111/cup.13846

Haghayeghi K, Robinson-Bostom L, Olszewski A, Jackson CL, Patel NR, Sewastianik T, Carrasco RD, Shanmugam V, Treaba DO. Aggressive CD4/CD8 Double-Negative Primary Cutaneous T-Cell Lymphoma With Dural Invasion: A Rare Presentation of Mycosis Fungoides? Am J Dermatopathol. 2021 Jan 1;43(1):63-66. doi: 10.1097/DAD.0000000000001725. PMID: 32675473. DOI: https://doi.org/10.1097/DAD.0000000000001725

Alnasser MA, AlKhawajah NM, AlQadri NG, Shadid AM, Alsaif FM. Erythrodermic CD4/CD8 Double-Negative Mycosis Fungoides: A Case Report. Case Rep Oncol. 2021 Mar 2;14(1):256-261. doi: 10.1159/000512822. PMID: 33776713; PMCID: PMC7983607. DOI: https://doi.org/10.1159/000512822

Kasinathan G, Sathar J. Disseminated mature T-cell phenotype CD4/CD8 double-negative mycosis fungoides with pleural involvement. Hematol Transfus Cell Ther. 2021 Sep 20:S2531-1379(21)00132-2. doi: 10.1016/j.htct.2021.07.004. Epub ahead of print. PMID: 34593365. DOI: https://doi.org/10.1016/j.htct.2021.07.004

Ballano Ruiz A, Bakali Badesa S, Gómez Mateo MC, Yus Gotor MC. Cytotoxic CD4/CD8 Double-Negative Mycosis Fungoides. Actas Dermosifiliogr. 2022 Feb;113(2):199-201. English, Spanish. doi: 10.1016/j.ad.2020.05.015. Epub 2021 Sep 17. PMID: 35244567. DOI: https://doi.org/10.1016/j.ad.2022.01.010

Wilmas KM, Aria AB, Landis LN, Chaitanya SK, Prieto VG, Duvic M. CD4/CD8 double-negative mycosis fungoides with large cell transformation and involvement of the lungs and leptomeninges. Dermatol Online J. 2022 Mar 15;28(2). doi: 10.5070/D328257394. PMID: 35670681. DOI: https://doi.org/10.5070/D328257394

Jawed SI, Myskowski PL, Horwitz S, Moskowitz A, Querfeld C. Primary cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome): part I. Diagnosis: clinical and histopathologic features and new molecular and biologic markers. J Am Acad Dermatol. 2014 Feb;70(2):205.e1-16; quiz 221-2. doi: 10.1016/j.jaad.2013.07.049. PMID: 24438969. DOI: https://doi.org/10.1016/j.jaad.2013.07.049

Vu BA, Duvic M. Central nervous system involvement in patients with mycosis fungoides and cutaneous large-cell transformation. J Am Acad Dermatol. 2008 Aug;59(2 Suppl 1):S16-22. doi: 10.1016/j.jaad.2007.09.025. PMID: 18625371. DOI: https://doi.org/10.1016/j.jaad.2007.09.025

Wain EM, Orchard GE, Mayou S, Atherton DJ, Misch KJ, Russell-Jones R. Mycosis fungoides with a CD56+ immunophenotype. J Am Acad Dermatol. 2005 Jul;53(1):158-63. doi: 10.1016/j.jaad.2005.01.133. PMID: 15965442. DOI: https://doi.org/10.1016/j.jaad.2005.01.133

Santucci M, Pimpinelli N, Massi D, Kadin ME, Meijer CJ, Müller-Hermelink HK, Paulli M, Wechsler J, Willemze R, Audring H, Bernengo MG, Cerroni L, Chimenti S, Chott A, Díaz-Pérez JL, Dippel E, Duncan LM, Feller AC, Geerts ML, Hallermann C, Kempf W, Russell-Jones R, Sander C, Berti E; EORTC Cutaneous Lymphoma Task Force. Cytotoxic/natural killer cell cutaneous lymphomas. Report of EORTC Cutaneous Lymphoma Task Force Workshop. Cancer. 2003 Feb 1;97(3):610-27. doi: 10.1002/cncr.11107. PMID: 12548603. DOI: https://doi.org/10.1002/cncr.11107

Vermeer MH, Geelen FA, Kummer JA, Meijer CJ, Willemze R. Expression of cytotoxic proteins by neoplastic T cells in mycosis fungoides increases with progression from plaque stage to tumor stage disease. Am J Pathol. 1999 Apr;154(4):1203-10. doi: 10.1016/S0002-9440(10)65372-2. PMID: 10233858; PMCID: PMC1866574. DOI: https://doi.org/10.1016/S0002-9440(10)65372-2

Imam MH, Shenoy PJ, Flowers CR, Phillips A, Lechowicz MJ. Incidence and survival patterns of cutaneous T-cell lymphomas in the United States. Leuk Lymphoma. 2013 Apr;54(4):752-9. doi: 10.3109/10428194.2012.729831. Epub 2013 Jan 7. PMID: 23004352. DOI: https://doi.org/10.3109/10428194.2012.729831

Pimpinelli N, Olsen EA, Santucci M, Vonderheid E, Haeffner AC, Stevens S, Burg G, Cerroni L, Dreno B, Glusac E, Guitart J, Heald PW, Kempf W, Knobler R, Lessin S, Sander C, Smoller BS, Telang G, Whittaker S, Iwatsuki K, Obitz E, Takigawa M, Turner ML, Wood GS; International Society for Cutaneous Lymphoma. Defining early mycosis fungoides. J Am Acad Dermatol. 2005 Dec;53(6):1053-63. doi: 10.1016/j.jaad.2005.08.057. PMID: 16310068. DOI: https://doi.org/10.1016/j.jaad.2005.08.057

Molloy K, Jonak C, Woei-A-Jin FJSH, Guenova E, Busschots AM, Bervoets A, Hauben E, Knobler R, Porkert S, Fassnacht C, Cowan R, Papadavid E, Beylot-Barry M, Berti E, Alberti Violetti S, Estrach T, Matin R, Akilov O, Vakeva L, Prince M, Bates A, Bayne M, Wachsmuch R, Wehkamp U, Marschalko M, Servitje O, Turner D, Weatherhead S, Wobser M, Sanches JA, McKay P, Klemke D, Peng C, Howles A, Yoo J, Evison F, Scarisbrick J. Characteristics associated with significantly worse quality of life in mycosis fungoides/Sézary syndrome from the Prospective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study. Br J Dermatol. 2020 Mar;182(3):770-779. doi: 10.1111/bjd.18089. Epub 2019 Jul 28. PMID: 31049926. DOI: https://doi.org/10.1111/bjd.18089

Shimauchi T, Sugita K, Nishio D, Isoda H, Abe S, Yamada Y, Hino R, Ogata M, Kabashima K, Tokura Y. Alterations of serum Th1 and Th2 chemokines by combination therapy of interferon-gamma and narrowband UVB in patients with mycosis fungoides. J Dermatol Sci. 2008 Jun;50(3):217-25. doi: 10.1016/j.jdermsci.2007.12.004. Epub 2008 Feb 19. PMID: 18243665. DOI: https://doi.org/10.1016/j.jdermsci.2007.12.004

Haruyama S, Sugita K, Kawakami C, Nakamura M, Tokura Y. Development of a prominent granulomatous eruption after interferon-gamma therapy in a patient with mycosis fungoides. Acta Derm Venereol. 2010 Mar;90(2):190-1. doi: 10.2340/00015555-0788. PMID: 20169308. DOI: https://doi.org/10.2340/00015555-0788

Trautinger F, Eder J, Assaf C, Bagot M, Cozzio A, Dummer R, Gniadecki R, Klemke CD, Ortiz-Romero PL, Papadavid E, Pimpinelli N, Quaglino P, Ranki A, Scarisbrick J, Stadler R, Väkevä L, Vermeer MH, Whittaker S, Willemze R, Knobler R. European Organisation for Research and Treatment of Cancer consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome - Update 2017. Eur J Cancer. 2017 May;77:57-74. doi: 10.1016/j.ejca.2017.02.027. Epub 2017 Mar 31. PMID: 28365528. DOI: https://doi.org/10.1016/j.ejca.2017.02.027

Hamada T, Sugaya M, Tokura Y, Ohtsuka M, Tsuboi R, Nagatani T, Tani M, Setoyama M, Matsushita S, Kawai K, Yonekura K, Yoshida T, Saida T, Iwatsuki K. Phase I/II study of the oral retinoid X receptor agonist bexarotene in Japanese patients with cutaneous T-cell lymphomas. J Dermatol. 2017 Feb;44(2):135-142. doi: 10.1111/1346-8138.13542. Epub 2016 Aug 20. PMID: 27543197. DOI: https://doi.org/10.1111/1346-8138.13542

Leuchte K, Schlaak M, Stadler R, Theurich S, von Bergwelt-Baildon M. Innovative Treatment Concepts for Cutaneous T-Cell Lymphoma Based on Microenvironment Modulation. Oncol Res Treat. 2017;40(5):262-269. doi: 10.1159/000472257. Epub 2017 Apr 20. PMID: 28423378. DOI: https://doi.org/10.1159/000472257

Ollila TA, Sahin I, Olszewski AJ. Mogamulizumab: a new tool for management of cutaneous T-cell lymphoma. Onco Targets Ther. 2019 Feb 7;12:1085-1094. doi: 10.2147/OTT.S165615. PMID: 30799938; PMCID: PMC6369856. DOI: https://doi.org/10.2147/OTT.S165615

Kim YH, Bagot M, Pinter-Brown L, Rook AH, Porcu P, Horwitz SM, Whittaker S, Tokura Y, Vermeer M, Zinzani PL, Sokol L. Anti-CCR4 monoclonal antibody, mogamulizumab, demonstrates significant improvement in PFS compared to vorinostat in patients with previously treated cutaneous T-cell lymphoma (CTCL): results from the Phase III MAVORIC Study. Blood. 2017 Dec 8;130:817. DOI: https://doi.org/10.1182/blood.V130.Suppl_1.817.817

Nabil Nagshabandi, K., Shadid, A., Shadid, A., & Almuhanna, N. K. (2024). CD4/CD8 double-negative mycosis fungoides: a review. Dermatology Reports. https://doi.org/10.4081/dr.2024.9908

Downloads

Download data is not yet available.

Citations